Qualification and Validation have big Weightage in the Regulatory Compliance and GMP. Qualification and Validation only can guarantee about the Product Safety, Integrity, Strength, Purity and Quality assurance.
Process Validation is Key important factor for the Pharmaceutical Industry to maintain Consistent Quality in product which claimed by the manufacturer.
Fluidized Bed Dryer
Principle of FBD
Construction of FBD
Working of FBD
Steps of Fluidization
Qualification of FBD
Design Qualification
Installation Qualification
Operational Qualification
Performance Qualification
References
According to new syllabus of PCI M.Pharm 1st sem. students can directly utilize this ppt for their study. As per PCI new syllabus QA STUDENTS find this ppt very use full.
Extensively used in pharmaceutical for product quality analysis. For trend analysis of product and steps of manufacturing it is widely used. By calculating cpk value any out of specification can be determined. It is more important tools to analyze from starting material to finished product
Qualification and Validation have big Weightage in the Regulatory Compliance and GMP. Qualification and Validation only can guarantee about the Product Safety, Integrity, Strength, Purity and Quality assurance.
Process Validation is Key important factor for the Pharmaceutical Industry to maintain Consistent Quality in product which claimed by the manufacturer.
Fluidized Bed Dryer
Principle of FBD
Construction of FBD
Working of FBD
Steps of Fluidization
Qualification of FBD
Design Qualification
Installation Qualification
Operational Qualification
Performance Qualification
References
According to new syllabus of PCI M.Pharm 1st sem. students can directly utilize this ppt for their study. As per PCI new syllabus QA STUDENTS find this ppt very use full.
Extensively used in pharmaceutical for product quality analysis. For trend analysis of product and steps of manufacturing it is widely used. By calculating cpk value any out of specification can be determined. It is more important tools to analyze from starting material to finished product
Presentation: TGA manufacturing principles update - Adoption of PIC/S Guide t...TGA Australia
2018 has posed many changes for the TGA regulated Pharmaceutical manufacturing industry with the TGA legislating version 13 of the PIC/S guide to GMP for medicinal products which included several changes to both the general chapters and the relevant Annexes. With the implementation transitioning through to the end of December, Manufacturers and Sponsors need to be informed and actively implementing these changes. Additionally, a draft version of Annex 1 has also been released which has the potential to significantly impact sterile manufacturing requirements.
Qualification of Dissolution Test Apparatus and Validation of Utility System this presentation will help to enhance your knowledge in validation and qualification area.
Q.R are planned and documented by an inspections of a review item
The review item may be a product, a group of related products or a part of a product
If the error identified earlier the cost of implication is less and the penalty for failing to conduct adequate reviews.
Documentation with respect to release of finished pharmaceutical productMadhuraNewrekar
Documentation is a crucial part of the quality assurance system and is needed in every aspect of pharmaceutical manufacturing. Important documentation with respect to final product release in pharmaceutical industry is explained in brief.
PHARMACEUTICAL CALIBRATION & VALIDATION.
What is Validation?
What is calibration?
What are the types of Validation ?
Validation and calibration Basic Difference
Presented at length on 23 April and 21 May 2017 at ICCBS, HEJ and Getz Pharma Auditorium, Karachi in a Discussion Forum of about 800 practicing university qualified professionals of various pharmaceutical manufacturing industries
Drug Discovery path
Pharma R & D –overview
Discovery & Development
Preclinical research
Clinical Trial
NDA and FDA Approval
Post marketing data
References
Optical Rotation and Polarimeter by Dr. A. AmsavelDr. Amsavel A
Isomers and enantiomers
Specific Optical Rotation
Polarimeter
Instrumentation and Operation
Factors affect the Optical Rotation
Calibration
Application Specifically Pharmaceutical Industries
Personal Hygiene for pharma industry-Dr. A. AmsavelDr. Amsavel A
Personal hygiene
Source of Contamination and control
GMP Requirement /Guideline
Procedures & Records
Protective Clothing & gowning
Health Examination
Hand wash – How and when
Training & Practice
by Dr. A. Amsavel
Awareness on Cancer
what are the causes for cancer
Terminology
Classification of Cancers
Signs and Symptoms
Stages of Cancers (TSM)
Types of Cancer Treatments
Surgery, Chemotherapy, Radiation Therapy etc
Side effects on treatment
Palliative care
FTIR SPECTROSCOPY,
Principle, Theory, Instrumentation and Application in Pharmaceutical Industry
IR Spectroscopy- Absorption Theory
Type of Vibrations & Vibration Energy level
FTIR Spectrophotometer-Instrumentation
Operation of the Spectrophotometer
Qualification & Calibration
IR Absorption by Organic compounds
Application
FDA citation in FTIR Analysis-Pharmaceutical Industries
UV -Vis Spectrophotometry- Principle, Theory, Instrumentation and Application...Dr. Amsavel A
UV -Vis Spectrophotometry- Principle, Theory, Instrumentation and Application in Pharmaceutical Industry Dr. A. Amsavel.
UV &Visible Spectroscopy-Absorption Theory
Electronic Transitions
Beer- Lambert Law
Chromophores & Auxochrome
Factors Influence the Absorption
UV-Vis Spectrophotometer-Instrumentation
Operation of the Spectrophotometer
Qualification & Calibration
Application
Handling of Refernce Standards_Dr.A.Amsavel Dr. Amsavel A
Definition
Requirements
Guidelines
Pharmacopiea
Types of Reference Standards
SOP for handling of Reference Standards
Qualification of Secondary Standards
Assigning Potency, Storage and Use
Documents & Records
Contamination Control in Cleanrooms_Dr.A. AmsavelDr. Amsavel A
Basic’s of Contamination
Sources of Contamination
Environment Specification
Elements of Cleanroom Design and Qualification
Definitions
Control of Contaminations
People, Cleaning, Environment & Material
Operation, Monitoring and Control
Documents and Records
Handling of Customer Complaint_Dr.A.AmsavelDr. Amsavel A
Reference Guideline
Definitions
GMP Requirement: 21 CFR § 211.198 and ICH Q7
Procedure for Handling of Complaints
Complaint Investigation
Remedial action and CAPA
Report preparation
Response to customer
Verification of CAPA effectiveness
Review of Complaints
Review of Quality Control Record and Analytical Data by Dr. A. AmsavelDr. Amsavel A
Review of Quality Control Record and Analytical Data
Objective and Requirement for Analytical data review
Role of Analyst and reviewer,
Procedure and checklist for review of records/data
Review of traceable /associated documents
Review of calibration, Reference standard record, sampling reports,
Review of Audit trail
Role of Analyst & Reviewer
Review of chromatograms& audit trail,
Data Integrity & Good Record Practice
FDA Citations
Volumetric Analysis
Titration Basics
Reaction, End point & Indicators
Types of Titrations
Acid – Base Theory & Principles
Acid Base titration
Non- Aqueous Titration
Precipitation Titration
Complexometric Titration
Oxidation- Reduction Titration
Calculation
General Information
Errors
Volumetric Analysis
Types of titration
Acid- Base Theory
Reaction, End Point & Indicators
Acid- Base titration
Titration curve
Non- Aqueous Titration
Precipitation Titration
Complexometric Titration
Oxidation- Reduction Titration,
Calculation. Errors
General Informations,
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
2. An Overview
Annual Product Quality Review (APQR)
Guidelines / Requirement
Responsibility
Procedure
Documents and Data Required
Preparation, evaluation and documentation
Eg. Trend Charts, process capability
Recommendation and Conclusion
3. Questions?
What is an Annual Product Review?
What is the objective of APR?
Who are all responsible?
How Procedure has to be prepared? How Procedure has to be prepared?
What are the data must be presented in an annual
product review?
How should an Annual Product Review be organized?
How to prepare the report ?
Recommendation and conclusion
4. APR, PQR or APQR
USA: “Annual Product Review”
Europe, the EU GMP Guideline uses the term "Product
Quality Review".
APQR should be conducted for all commercial product. APQR should be conducted for all commercial product.
APQR should confirm the State of Control of product,
manufacturing process, and quality.
Requirement or expectations are almost same
There are few differences, it is explained subsequently
5. Purpose of Annual Product Review
The purpose of Annual Product Review is to verify the consistency
of the process, to assess trends, to determine the need for
changes in specification, production, manufacturing and/or control
procedures and to evaluate the need for revalidation. This is toprocedures and to evaluate the need for revalidation. This is to
be conducted for each commercial product.
Annual Product Reviews are important for communication
between manufacturing, quality and regulatory Affairs, to enable
quality improvement processes. Content and management of
Annual Product Reviews must be established according to GMP
requirement / directive.
6. Reference / Guidelines
All GMP Guidelines refer the requirement of APQR
CFR 211.180 (e)
ICH Q7 (2.5) for API
PICS (PP-PE 009-14 Part I & PE 009-12 API-Part II) PICS (PP-PE 009-14 Part I & PE 009-12 API-Part II)
WHO- GMP TRS 986- Annex-2 (PP) TRS957,
Annex 2 (API).
EU GMP EudraLex - Volume 4 : Part-2 GMP for APIs and
Part-1, Volume 4 : EU GMP for Medicinal products
Chapter 1
7. Requirement: 21 CFR 211.180 (e)
• US FDA requirement for APR is to evaluating, at least annually, the
quality standards of each drug product to determine the need for
changes in drug product specifications or manufacturing or control
procedures.
the manufacturing controls (Critical process parameter, quality attributes
yield etc…)yield etc…)
evaluate the compliance status of the manufacture and to identify areas
of improvement or need for revalidation
A review of a representative number of batches, whether
approved or rejected, and records associated with the batch
A review of complaints, recalls, returned or salvaged drug
products, and investigations conducted under Sec. 211.192 for
each drug product.
8. Requirement: ICH Q7 for APIs
2.5 Product Quality Review:
2.50 Regular quality reviews of APIs should be conducted with the
objective of verifying the consistency of the process. Such reviews
should normally be conducted and documented annually and should
include at least:
A review of critical in-process control and critical API test results;
A review of all batches that failed to meet established specification;
A review of all critical deviations or non-conformances and related
investigations;
A review of any changes carried out to the processes or analytical
methods;
9. Requirement: ICH Q7 for APIs
A review of results of the stability monitoring program;
A review of all quality-related returns, complaints and
recalls; and
A review of adequacy of corrective actions A review of adequacy of corrective actions
2.51. The results of this review should be evaluated and an
assessment made of whether corrective actions or any
revalidation should be undertaken. Reasons for such
corrective action should be documented. Agreed corrective
actions should be completed in a timely and effective
manner.
10. Requirement: EU GMP
EU Guidelines to Good Manufacturing Practice: Medicinal Products
for Human and Veterinary Use ; Part I Quality Management
Product Quality Review
1.5 Regular periodic or rolling quality reviews of all licensed medicinal
products, including export only products, should be conducted with the
objective of verifying consistency of the existing process, the suitability
of current specifications for both starting materials and finished product
to highlight any trends and to identify product and process
improvements. Such reviews should normally be conducted and
documented annually, taking into account previous reviews, and should
include at least
11. Requirement: EU GMP
A review of starting materials and packaging materials used for
the product, especially those from new sources
A review of critical in- process controls and finished product
results
A review of all batches that failed to meet established
specification(s) and their investigation.
A review of all significant deviations or non-conformances ,
their related investigations, and the effectiveness of resultant
corrective and preventative actions taken
Note: The requirements mentioned in red is different from ICH Q7 and same as WHO
TRS and PICS guideline
12. Requirement: EU GMP
A review of all changes carried out to the processes or
analytical methods
A review of the results of the stability monitoring programme
and any adverse trendsand any adverse trends
A review of all quality- related returns, complaints and recalls
and the investigations performed at the time
A review of Marketing Authorisation variations submitted/
granted/ refused, including those for third country (export
only) dossiers.
13. Requirement: EU GMP
A review of adequacy of any other previous product process or
equipment corrective actions. For marketing authorisations like
new, variation or post-marketing commitments
The qualification status of relevant equipment and utilities, e.g.
HVAC, water, compressed gases, etc
A review of Technical/Quality Agreements to ensure that they
are up to date.
14. Benefit or Use
Meeting the Regulatory Commitments and Requirements
Help to minimize the OOS results and deviations
Minimize the risk of Rework or Reprocessing
Decrease downtime
Increase productivity
Decrease the Risk of Product Recalls
Improve communication between production,
engineering, quality and regulatory functions
15. Responsibilities
Responsibilities lies with QA
Establish an SOP with responsibility and process of APQR
Individual departments have to provide the data and participating in
the APQR process.
Reviews should normally be conducted and documented
The Quality Unit, as the central position, should request this review
and coordinate the necessary work. Can develop format/ check list
to get information.
Production, Engineering , Maintenance , Purchase, etc. are also
need to be involved.
Senior Quality Management must approve the APQR.
16. SOP for APR
Written procedures shall be established and it must be
followed ;
Procedure must cover at least one-year rolling period. Can be on calendar
year
The review all products manufactured and should be completed within 60 The review all products manufactured and should be completed within 60
calendar days
In case product not manufactured in the year of review, shall review stability
and complaint, Recall & Returns etc.
1. Review all batches manufactured (accepted /rejected /destroyed)
2. The review of all batches which fail to meet specification and the review of
critical deviations in the production, Laboratory facility etc
3. Assessment of data, documents and electronic records in the review
17. SOP for APR
4. Review of the starting materials used and change of vendor of KSM
5. Review of the In-process control test results, quality attributes of
intermediate and final product.
6. Review of process parameters and output or yield
7. Review of all quality related returns, complaints and recalls and the7. Review of all quality related returns, complaints and recalls and the
investigations performed
8. Review the stability data and adverse trends if any
9. Result of verification of reserve samples
10. Equipment addition or retired, Qualification/requalification, calibration&PM
11. Review of any changes carried out in the processes equipment ,
specifications or analytical methods, facility,
18. SOP for APR
12. Review of action taken for the recommendation of the previous
year PQR
13. Review of adequacy of corrective actions implemented and
effectiveness
14. Review the critical utilities like HVAC, water, compressed gases
o Result of Environment monitoring/ Bio-burdon
o Water test results- conductivity, TOC trend etc
o If it is common utilities, it can be documented separately.
15. Review of technical agreements and ensure it is updated.
All the above details shall be covered in the SOP. Prepare trend
data, statistical analysis with conclusion and recommendation
19. Review and Preparation of APR
Collect the data and tabulate the selected parameters,
for review and documentation. Example
o Key starting material /Critical material
o Critical quality parameters of finished product/blended
o Batch No, test parameters, test result of intermediates & API
o Critical in-process controls & test results, process parameters
o No. of batches manufactured, and corresponding yields
o No. Or % of batches rejected, reworked or reprocessed
o No. of Batches under OOS, non-conformance / deviation
o Quantity or No. of Complaints, returns etc
20. Review of Documents & System
Data collection and review
Manufacturing instructions and packaging procedures
Changes in the process and validation status after change
Batch Production Records
Process parameters: actual and standard
IPC test data, deviations, Yield, Cpk, IPC test data, deviations, Yield, Cpk,
Equipments change
Environment monitoring
Quality Control Data
Changes to specifications or methods
Validation status of the test methods
Analytical Instruments& equipment Qualification, calibration
Deviation or incident
21. Review of Documents & system
Data collection and review
Quality Management System:
Deviations, OOS, Failure cause analysis
Customer complaint, Returns, recalls
Reprocess, rework / salvage of material
Vendor status :
Change of vendor, qualification and approval
Deviations, rejections of raw material
Facility :
Change of facility, utility , HVAC, compressed gases etc
Requalification of HVAC, temperature, differential pressure
environment monitoring - bio-burden and deviation if any
22. Review and Preparation of APR
Review of Stability data / Hold time data
Adverse trend if any
Changes to packaging material or Process
Review of Water system: Changes, qualification, chemical andReview of Water system: Changes, qualification, chemical and
microbial trend, deviation if any
Review of technical agreements with contact manufacturing, testing
Lab and service providers ensure it is updated
Result of verification of reserve samples and report deterioration if
any
Regulatory: Issues and annual update requirement if any
23. Conclusion and Recommendations
Prepare the detailed report for each elements and present the required
data, trend chart , review all the data, report the observation based on
the findings. Report the conclusion and recommendation based on the
overall review.
Observations/Recommendations and conclusion Observations/Recommendations and conclusion
A conclusion statement must be written to assess if the product
consistently meets its quality attributes, and if not, what actions need to
be taken,
The results of the APR must be evaluated and an assessment made
whether corrective or preventive action or any re-validation is necessary.
Rationale for such CAPAs must be documented.
24. Conclusion and Recommendations
State of validation, consistency of process parameter & quality attributes.
Any spike or OOT in the data have to explained and justified
Following are the examples for recommendation, but not limited to:
Product process improvement
Analytical method improvements Analytical method improvements
Revision of specification
In-process or final product specification review
Revalidation, Requalification
Product recall or withdrawal
New packaging
Training
Vendor control
Calibration and maintenance
25. How to Collect Data, Preparation,
Review and Documentation of APR:
A Practical ApproachA Practical Approach
26. Organizing Documents
List the documents and Records to be reviewed
Arrange all the relevant documents, BPRs, Test records log
books, calibration, computer system, data from external
source as required
QMS documents, deviations, failures/ nonconformity,
Complaints, investigation and CAPA reports Change control ,
Returns, Recalls, etc
Validation, Qualification, Stability data, Utility data, etc
Prepare the template for entering the data
Use check list to prevent the missing data
27. Check List for APQR
Is there any outstanding Validation commitments from last PQR
or corrective and preventive action plans?
Is process in a validated state or revalidation needed ?
Is the qualification / Requalification of Equipment adequate?
Are there any significant findings from the data/trend in the
manufacturing process, starting materials, or packaging materials ?
Are all change controls implemented, and closed?
Any annual update to be submitted regulatory agencies?
Are all change controls, deviations, OOS investigation, complaints
are reviewed, investigated, CAPA implemented, and closed?
Is corrective/ preventive action is adequate and effective ?
28. Check List for APQR
Are there any significant findings related to the following
changes performed ?
specifications or test methods ?
deviations and non- conformances ?
out of specification results ? out of specification results ?
rejected batches, quality-related returns, customer complaints, or
recalls ?
the stability data monitoring ?
retain sample examination ?
Are all post- marketing commitments to Authorities met ?
Are all the Technical Agreements in place and up-to-date ?
29. Review of Deviations
Review of “Deviations from the Validated state”, investigation
and CAPA
A review of all batches that failed to meet established
specification(s) and their investigation
Significant/critical deviations, Out of Specification Results and Significant/critical deviations, Out of Specification Results and
related failure investigations.
Review for adequacy and effectiveness of corrective and
preventative actions
Changes effected and variations during the period (e.g. process,
suppliers, equipment, critical utilities)
Changes of product specifications or methods (e.g. analytical
changes, and results)
30. Preparation of Trend Charts
Trend Analysis: Perform trend analysis for the result of in-process,
release test parameters and results of the stability monitoring with graphic
representation with basic statistical data.
Prepare control chart, other types of chart
Appropriate statistical tools may be used to assess process capability for Appropriate statistical tools may be used to assess process capability for
large number of batches.
Mean, maximum, minimum, standards deviations, six sigma, %RSD
If any drift in process, out of trend, evaluate the causes and take
appropriate action and improve performance
Review specifically at recurring causes and identify appropriate actions to
reduce the frequency and improve performance.
33. Process Capability
Normal Distribution:
µ ± σ = 68.26%
µ ± 2σ = 95.44%
µ ± 3σ = 99.73%µ ± 3σ = 99.73%
µ is mean value; σ is standard
deviation
The capability of the process to
meet the specifications
determined by stability of the
process, the range of variation
and the process aim point
34. Normal distribution
Normal
Process Capability for strength
LSL = 114.0, Nominal = 115.0, USL = 116.0
24
Histogram follows NORMAL DISTRIBUTION Process
meets the Specification, consistent and capable
Normal
Mean=114.978
Std. Dev.=0.238937
Cp = 1.41
Pp = 1.40
Cpk = 1.38
Ppk = 1.36
K = -0.02
114 114.4 114.8 115.2 115.6 116
strength
0
4
8
12
16
20
24
frequency
DPM = 30.76
35. Process Capability Index
Process Capability Index Calculation;
Cpk = (SU – SL)/ 6 σ (σ- Standard deviation,
If Specification is one sided
Cp
SU- Upper spec limit
SL- Lower spec limit
X- Base value of one side
(σ- Standard deviation,
Cpk = (SU – X)/ 3 σ
Cpk = (X - SL)/ 3 σ
(σ- Standard deviation,
# CPk Value Process Capability
1 1.33 ≤ Cpk Satisfiable enough
2 1.00 ≤ Cpk < 1.33 Adequate
3 Cpk < 1.00 Inadequate
36. Process Capability Index (Cpk)
Assumption- Chemical process-A
give Yield range:100 -120kg,
Standard deviation : 3.4 and mean
is 12kg. Calculate the process
capability
20
Cp = -------
6*3.4
Assumption- Chemical process-A give
Yield range: 100 -120 kg; Mean is
111kg and standard deviation : 2.2.
Calculate the process capability
20
Cp = -------
6*2.2Cp = -------
6*3.4
Cp= 0.98
Process in not capable, there is
inconstant
Cp = -------
6*2.2
Cp = 1.52
Process is capable & constant